Phase 1B Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children With Neutropenia

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 23

Inclusion Criteria

1. Children of either sex and of any race, 3 months to <18 years of age.;2. Subjects* parent or legally authorized representative must be willing to give written informed consent. Assent will be obtained from minors according to institutional practices.;3. Subjects must have documented or anticipated neutropenia (ANC <=500/mm3 [0.5 x 109/L]) expected to last for at least 7 days and only in the following clinical situations:
a. Acute leukemia (including new and relapse),
b. Myelodysplasia,
c. Severe aplastic anemia,
d. Autologous HSCT recipients,
e. High risk neuroblastoma,
f. Advanced stage non-Hodgkin*s lymphoma.
g. Recipients of allogeneic HSCT during the pre-engraftment period
(neutropenia period).;4. Male and female subjects of child-bearing potential must agree to use a medically accepted method of contraception throughout the study and for at least 30 days after stopping the medication, unless they are surgically or medically sterile or agree to abstain from sexual intercourse. Acceptable methods of contraception include 2 of the following:
a. Condoms (male or female) with spermicide,
b. Diaphragm or cervical cap (if acceptable according to local standard of care) with spermicide
(females),
c. Hormonal contraceptives or intrauterine device with spermicide (females).

Exclusion Criteria

1. Subjects with proven IFI, as defined by the MSG/EORTC criteria (see Appendix 3), prior to study entry.;2. Subjects with Grade 3 or Grade 4 nausea and/or vomiting at Screening.;3. Subjects who have received POS within the past 10 days prior to Screening.;4. Subjects receiving prohibited drugs (please refer to Table3).;5. Subjects whose laboratory tests are outside normal limits, as follows:
a. AST or ALT >5 times the upper limit of normal (ULN)
b. Serum total bilirubin >2.5 x ULN
c. Calculated creatinine clearance <30 mL/min. Creatinine clearance will be calculated using the
following equation: Creatinine clearance = k*height (cm)/serum creatinine (mg/dL)
Where k = 0.45 for a full term baby less than 1 year old; 0.55 for children up to 12 years old; 0.55
for females between the ages of 13 and 21 years; 0.7 for males between the ages of 13 and 21
years.;6. Subjects with QTc prolongation:
a. Symptomatic QTc prolongation >450 msec (males) or >470 msec (females)
b. Any QTc prolongation of >500 msec;7. Subjects who are unable to receive study drug enterally.;8. Female subjects who are pregnant, intend to become pregnant during the course of the study, or are breast-feeding.;9. Subjects with a history of anaphylaxis attributed to the azole class of antifungal agents.;10. Subjects with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study, including receiving less than 7 days of POS.;11. Subjects who have already participated in this study or are participating in any Phase 1 clinical study or any study for a medication that has not yet received regulatory approval. Note: If the medication has received a regulatory approval for use in adults, then the medication would be considered to have received a regulatory approval for the purpose of this criterion. Any medication received by eligible subjects must also be aligned with the protocol guidance for prohibited medications (Table 3). ;12. Subjects who are part of the study staff personnel or family members of the study staff personnel.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to evaluate the PK of POS administered<br /><br>orally at three dosage levels to immunocompromised children with neutropenia or<br /><br>expected neutropenia aged 3 months to <18 years.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objective of this study is to evaluate the safety and<br /><br>tolerability of POS administered orally at three dosage levels to<br /><br>immunocompromised children with neutropenia or expected neutropenia aged 3<br /><br>months to <18 years, and to compare the exposures to POS in pediatric subjects<br /><br>to those from an adult population with similar underlying conditions.</p><br>